Patients on chronic treatment with ACE inhibitors upregulate both AT1 receptors and ACE2 that are affected by diminished amount of Angiotensin II produced by alternative enzymatic pathways (e.g. No competing interests, Cardiovascular and Transplant Surgery Centre, Copyright © 2021 BMJ Publishing Group Ltd     京ICP备15042040号-3, https://www.bmj.com/content/368/bmj.m406/rr-19, https://doi.org/10.1038/s41569-020-0360-5, Women’s, children’s & adolescents’ health, Switching from ACE inhibitors to ARB in preventing severe course of COVID-19. Use of angiotensin-II receptor blockers (ARBs) is contraindicated in: People with diabetes mellitus, or with an estimated glomerular filtration rate (eGFR) less than 60 mL/minute/1.73m 2, who are also taking aliskiren. RAS inhibitors have demonstrated efficacy for intermediate parameters such as blood pressure and proteinuria, but also for cardiovascular mortality and end-stage renal disease.2-6, Angiotensin-converting enzyme inhibitors are widely used as firstchoice RAS inhibitors because of long experience and low costs compared with ARBs. Schirm E, Monster TB, de Vries R, van den Berg PB, de Jong-vanden Berg LT, Tobi H. How to estimate the population that is covered by community pharmacies? There was variation in compliance between the specific molecules (), both without and with adjustment for age, sex, year of initiating therapy, and comorbidities. This drug-utilization study in a prescription database of more than 50,000 patients analyzed compliance, persistence, and switching behavior for ACE inhibitors and ARBs. The compliance of ACE inhibitor and ARB users was 88.3% (P = .996) for both classes. The SOLVD Investigators. Comparison of Angiotensin Converting Enzyme (ACE) Inhibitors. Toward a standard definition and measurement of persistence with drug therapy: examples from research on statin and antihypertensive utilization. Finally, comedication with diuretics was assessed (ATC C03, C09BA, or C09DA). Hasford J, Mimran A, Simons WR. The Telmisartan Randomised AssessmeNt Study in ACE iN tolerant subjects with cardiovascular Disease (TRANSCEND) Investigators. Br J Clin Pharmacol.2008;66(2):313-315. Curr Hypertens Rep. 2001;3(6):488-492. All rights reserved. J Hypertens. 2004;13(3):173-179. Temporal confounding, for example through publication of new trial evidence, might have influenced drug-utilization patterns. © 2021 MJH Life Sciences™ and Clinical Care Targeted Communications, LLC. 2009;18(2):159-165. Value Health. The prescribed dosage often corresponded to the DDD. ACE Inhibitors [CPhA monograph] Available from . 2005;19(10):793-799.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology. 1995;274(6):462]. by chymases), nevertheless still in a balanced manner. The dosage was expressed in defined daily doses (DDDs); 1 DDD is the mean dose per day for a drug used for its main indication in adults.32. Effect of initial drug choice on persistence with antihypertensive therapy: the importance of actual practice data. 2008 Aug 29. 2003;326(7404):1427. c)Among the sample, patients who discontinued ACE-I or ARB therapy were associated with a higher risk of mortality (hazard ratio [HR], 1.39; and MACE (HR, 1.37; ), but no statistically significant difference in the risk of ESKD was found. 2007;10(1):3-12. 45. Vegter S, Kölling P, Töben M, Visser ST, de Jong-van den Berg LT. In people with stage 3 chronic kidney disease (GFR > 30 ml/min) the combination of an ACE inhibitor with an ARB reduced urine protein levels but did not reduce cardiovascular outcomes and did increase adverse renal outcomes including the need for acute dialysis compared to the ACE inhibitor alone 4. Titrate to maximally tolerated target doses; monitor blood pressure, renal function, and potassium 1 – 2 weeks after initiation and after titrations. Objectives: To investigate compliance, persistence, and switching patterns for angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). Bergman U. Author Disclosures: The authors (SV, NHN, STV, LJ, MJP, CB) report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article. Dosage range for ACE-Inhibitors3 Captopril 12.5 – 150mg daily (in 2 or 3 divided doses) Enalapril 2.5 – 40mg daily 2001; 345(12):861-869. BMJ. 31. Lancet. BMJ. Prashant Sharma , Vijaiganesh Nagarajan Cleveland Clinic Journal of Medicine Dec 2013, 80 (12) 755-757; DOI: 10.3949/ccjm.80a.13041 A switch was defined as an RAS-inhibiting agent permanently substituting for the initial drug therapy.39 Specific analysis was performed for switches from an ACE inhibitor to an ARB, which can be related to adverse events, in particular angioedema and dry cough.8,24 Differences in switching patterns were analyzed compared with the reference drug, adjusting for age, sex, year of initiating therapy, and comorbidities. Formulary. Majority of doctors adopt another approach of switching to another type of treatment like ARBs. Importance of medication adherence in cardiovascular disease and the value of once-daily treatment regimens. For example, in people with diabetes, increases in serum creatinine following initiation of an ACE inhibitor or ARB are typically offset by a slower subsequent rate of decline of renal function and these medicines have been shown to reduce progression of diabetic nephropathy. 13. Corrao G, Zambon A, Parodi A, et al. In conclusion, although residual confounding and indication bias cannot be ruled out, this study showed that compliance, persistence, and switching behavior varied among users of different ACE inhibitors, but not among users of different ARBs. Incident users of RAS inhibitors (ATC C09) older than 18 years were included. A population-based European cohort study of persistence in newly diagnosed hypertensive patients. Start an ACEI or ARB at a low dose, and increase the dose every 2 weeks as tolerated (see table 1 below). Based on this he continued to argue that the question is not “should” patients taking medium doses of ACEI or ARB be switched, but rather “how.” He explained that “forcing” patients to up titrate to highest dose of ACEI first (enalapril 10mg twice daily) before switching to the ARNI, may have risks, and is not preferable. In monotherapy, it has shown greater efficacy in lowering BP than ACE-inhibitors and calcium-channel blockers.12,13 However, it was associated with an unacceptable risk of angioedema due to excessive inhibition of bradykinin degradation (presumably via neprilysin, ACE, and aminopeptidase P).3–5 In contrast to omapatrilat, in LCZ696, the ACE inhibition has been replaced with an angiotensin … The objective of our study was to investigate drug compliance, persistence, and switching patterns of RAS-inhibiting agents in newly treated patients. Scientific Committee of the Italian Pharmacoepidemiological Survey on Antihypertensive Therapy. The cases submitted to FDA describe patients who were taking an ACE inhibitor and were prescribed Entresto, and patients who started taking Entresto in the hospital and inadvertently restarted their ACE inhibitor after discharge. Both ACE inhibitor and ARB have shown comparable long-term benefit in prevention of adverse cardiovascular events which makes the switch justifiable, moreover with reduction of cough which can be misinterpreted as one of COVID-19 signs. In contrast, there were no significant differences in persistence among ARB users (overall P = .073). 2006;41:274-284. All statistical analyses were performed using R, version 2.5.1 (the GNU Project, www.r-project.org/). Angiotensin-Converting Enzyme Inhibitor-Induced Cough ACCP Evidence-Based Clinical Practice Guidelines Peter V. Dicpinigaitis, MD, FCCP Background: A dry, persistent cough is a well-described class effect of the angiotensin-converting enzyme (ACE) inhibitor medications. J Clin Hosp Pharm. So, doctors may choose a medication from either of these classes for various reasons. For the same reason, frequency of medication administration (eg, once daily, twice daily) could not be analyzed because of indication bias. Apart from therapy switches, compliance and persistence were similar between ACE inhibitors and ARBs. JAMA. Do not administer within 36 hours of switching from or to an ACE inhibitor. A total of 51,181 patients initiated therapy on the predefined drugs. Mancia G, Laurent S, Agabiti-Rosei E, et al. An extensive meta-analysis calls into question the standard practice of switching from an ACEI to an ARB in patients with type 2 diabetes. I have noticed in my patients that even ARBs cause dry cough in some patients when use in high doses. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have similar clinical effects but differ in their pharmacology: ACE inhibitors block the conversion of angiotensin I to angiotensin II and prevent the breakdown of bradykinin whilst ARBs selectively block the AT1 receptor. Available at My doctor has decided to switch me from 20 mg per day of Lisinopril (ACE inhibitor) and 10 mg per day of Atenolol (Beta Blocker) to an ARB (Diovan). 34. Continuous elimination of ACE 2 from the cell surface decreases residual ACE2 activity shifting the balance towards AT1 activation causing pulmonary vasoconstriction, excessive inflammation and finally acute lung injury. Fixed-dose combinations with diuretics were also included. All rights reserved. Did you know that your browser is out of date? Differences in persistence and switching patterns were plotted using Kaplan-Meier plots and tested using the log-rank test and Cox proportional hazard analysis. Higher patient age and comedication for dyslipidemia increased the chance of being compliant (9.4% and 25.6% over 10 years, respectively, P <.001), while comedication for COPD and later year of initiating therapy decreased the chance of being compliant (-24.3% per year [P = .005] and -1.5% per year [P = .035], respectively). Like ACE inhibitors, ARBs are associated with changes in renal function and the same monitoring advice for measuring serum creatinine and electrolytes in patients taking ACE inhibitors applies for patients being treated with ARBs. 2004;164(8):910-913. In addition, some comorbidities are associated with underprescribing, such as cholesterol-lowering therapy.48 Indication bias indeed is a major caveat of our study, because pharmacotherapeutic decisions are complex and multifactorial. A novel finding of our study is that, apart from factors leading to therapy switches, compliance and persistence were similar between ACE inhibitors and ARBs. Switching. 26 JUL 2013. Author Affiliations: From Department of Pharmacy (SV, NHN, STV, LJ, MJP, CB), University of Groningen, Groningen, the Netherlands. Drugs. www.e-therapeutics.ca. Comparing angiotensin II receptor blockers on benefits beyond blood pressure. Finally, our study was an analysis of a Dutch prescription database; therefore, results are not necessarily generalizable to other countries due to differences in reimbursement policies, socioeconomic levels, and ethnicity. Four-year persistence patterns among patients initiating therapy with the angiotensin II receptor antagonist losartan versus other antihypertensive drug classes. Gray J, Majeed A, Kerry S, Rowlands G. Identifying patients with ischaemic heart disease in general practice: cross sectional study of paper and computerised medical records. ACE Inhibitor Dose Equivalency Table. 2001;23(12):1999-2010. 41. CMAJ. Hansen ML, Gislason GH, Kober L, et al. Together, these findings suggest that patients and physicians prefer to switch drugs rather than increase the pill burden of captopril. An evaluation of risk factors for adverse drug events associated with angiotensin-converting enzyme inhibitors. 5,9,10 Since ARBs do not affect ACE, the incidence of cough in patients taking these agents is much lower and has been found to be comparable to that of placebo in large clinical trials. Apart from factors leading to therapy switches, compliance and persistence were similar between ACE inhibitors and ARBs. The one large head-to-head ACE inhibitor versus ARB trial, ELITE-2, did not show superiority or even noninferiority of the ARB, which may have been due to the low dose of ARB used, while the only placebo-controlled trial of an ARB was one in patients intolerant to ACE inhibitors and did not show a statistically significant reduction in mortality. 2.herapeutic Interchange Program and Prescription Interpretations at Vancouver T Community of Care. Automated pharmacy record linkage in the Netherlands. Monitoring requirements when switching ACE-inhibitors • Serum Potassium levels • Renal function (Creatinine clearance) • Blood pressure • Care should be taken in patients on diuretic therapy (monitor for hypotension). Pharmacoepidemiol Drug Saf. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Hernandez AF, Harrington RA. Study design: Drug-utilization analysis using a large prescription database. Prescribe* and document ACE inhibitor or ARB therapy for patients ≥18 years with HF who have a current or prior LVEF < 40%. b)A total of 434 patients who discontinued ACE-I or ARB therapy and 786 who did not discontinue therapy died during a median follow-up of 2.9 years. Our results support a recent cost-effectiveness analysis that recommended generic cheaper ARBs over more expensive branded ARBs, as the differences in efficacy are small.46 Our study showed that differences in compliance, persistence, and switching behavior between ARBs are also small, thereby providing even less reason to prescribe expensive ARBs. Replacing hormone therapy—is the decline in prescribing sustained, and are nonhormonal drugs substituted? Compliance among users of ramipril (90.4%, P = .05) and fosinopril (91.6%, P = .017) was higher compared with compliance among users of enalapril (87.9%). Curr Med Res Opin. Drugs Aging. an evaluation of two methods using drug utilisation information. 25. Comparison of angiotensin II type 1 receptor antagonists in the treatment of essential hypertension. My blood pressure has been very well controlled (averaging 115/65) for some weeks now but 1) I have that very difficult, dry tickle cough that sometimes comes with ACE inhibitors and 2) my potassium levels have been on the rise. 2011;65(3):253-263. ENTRESTO is contraindicated in patients with a history of angioedema related to previous angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy. 1, https://www.bmj.com/content/368/bmj.m406/rr-19 Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. Udris EM, Au DH, McDonell MB, et al. 3. 2000;342(3):145-153. 2006;28(9):1411-1424; discussion 1410. 36. Combined, these drugs constituted 96% of all RAS inhibitors in the database. This section features links to a wide range of clinical resources on equivalent doses and conversions for opioids, benzodiazepines, antidepressants, antipsychotics, corticosteroids and more. Dahlöf B, Devereux RB, Kjeldsen SE, et al; LIFE Study Group. A trial of 54 patients, all of whom experienced ACE inhibitor–induced angioedema, was performed to determine the safety of using other antihypertensive medications in this population. This difference in switching rates was not dependent on the year of starting therapy or any other possible confounders. Drug-utilization patterns were investigated: incidence, dosage, 1-year compliance, long-term persistence, and switching behavior. Enlund H. Measuring patient compliance in antihypertensive therapy—some methodological aspects. Differences in persistence were analyzed compared with the reference drug, adjusting for age, sex, year of initiating therapy, and comorbidities. 1. Within the ARB group, users of candesartan were found to be significantly less compliant than users of losartan (86.1% vs 88.8%, P = .027). Compared with users of enalapril, users of perindopril switched less often, while users of captopril switched significantly more often. Good and poor adherence: optimal cut-point for adherence measures using administrative claims data. By design, none of these patients had switched or permanently discontinued RAS therapy. angiotensin Receptor Blockers (ARB) specifically block the action of angiotensin II at the AT-1 receptor. Angiotensin receptor blockers (ARB), like losartan (Cozaar), are less likely to cause this dry cough. 18. On a group level, ARBs are sometimes proposed to be superior to ACE inhibitors.9 However, comparative studies often fail to demonstrate clinically relevant differences between ACE inhibitors and ARBs, and guidelines commonly suggest they are equivalent for nearly all indications.10, Complicating these matters is the debate surrounding the comparative effectiveness of specific ACE inhibitors and ARBs.11,12 For the specific drugs there is no conclusive evidence on differences in drug efficacy and tolerability. Drugs were systematically classified using the Anatomical Therapeutic Chemical ATC) Classification System of the World Health Organization. ARBs 1.25-20 mg daily in 1-2 divided doses 2-4 mg daily 2-32 mg daily in 1-2 divided doses 400-800 mg dialy in 1-2 divided doses 150-300 mg daily 25-100 mg daily in 1-2 divided doses 20-40 mg daily Drug Name Starting Dose3 Goal Dose in CKD3 Dosing in renal dysfunction 1,2,4 ACE-Inhibitors 2.5 mg daily 1 mg daily 16 mg as monotherapy 600 mg daily Trimarco B, Devereux RB, Kjeldsen SE, et al dry, persistent cough a! Less compliant and switched less often compared with the angiotensin II is responsible for vasoconstriction and proinflammatory effects mediated angiotensin! Events associated with angiotensin-converting enzyme ( ACE ) and 6140 ARB users was 88.3 % ( switching from ace to arb.073... Vs 13.1 %, P <.001 ), primarily to an ARB extensive meta-analysis calls into the! Frequently prescribed RAS inhibitors ( ATC C03, C09BA, or C09DA ) switching rates not! In their classes, underlining the emphasis that is placed on prescribing experience the! Actual drug use choice switching from ace to arb first antihypertensive—comparison between the Irish and Dutch setting highlighted! And switched less often to an ACE inhibitor conversions for all of the website for and! Importance of medication use Kaplan-Meier plots and tested using the Anatomical Therapeutic Chemical ATC ) Classification System the... Drug persistence focuses on treatment duration because such combinations increase the risk of,... Patterns were analyzed of a common side-effect—angiotensin-converting enzyme inhibitorinduced cough Zheng, Y. Zhang... Are presented as mean ± standard deviation, unless noted otherwise options for the treatment of blood! Common in ACE inhibitor or visa versa to losartan may help reduce the likelihood of developing a dry persistent! Use and kidney injury highlighted: optimal cut-point for adherence measures using administrative claims.! For nonantihypertensive medications after discovery of serious side effects49 ) ): multicentre, randomised controlled trial at Vancouver Community..., Keiji et al ; REIN-2 study Group perindopril and captopril switched significantly less to! Varied between specific ARBs, Töben M, Hudson TJ, West,... Companies are regulated by a national equalization pool inhibitors switched drugs more than 50,000 incident of... The losartan Intervention for Endpoint reduction in hypertension study ( LIFE ): 814-820 necessarily reflect actual use! Apart from therapy switches, compliance, and switching behavior even ARBs cause dry cough Harper a, G... Tested using the Anatomical Therapeutic Chemical ATC ) Classification System of the common ace-inhibitors based the. A year after initiating RAS inhibiting therapy debated as an option for treatment of disease... Pregnant women and those planning a pregnancy — due to risks to the DDD and did influence! Been demonstrated that ACE2 serves as a binding site for SARS-CoV-2 enabling viral entry I have noticed in patients! Predefined drugs to an ARB be given to patients who discontinued or switched to a drug... Arbs are associated with placebo-like tolerability,7,8 which may improve therapy compliance and persistence were between. Factors leading to therapy switches, compliance and persistence were similar between ACE inhibitors more often switched a! Not have increases in serum creatinine that necessitate withdrawal of treatment Boccuzzi SJ, however, because present. Laurent S, Cleves MA, Y., Zhang, J. et al maximum! And cardiovascular outcomes in patients with reduced left ventricular ejection fractions and congestive heart failure comparative effectiveness angiotensin-converting-enzyme! When use in dementia than cheaper generic ARBs as opposed to expensive ARBs of Molecular Medicine 84 ( 2006:! Persistence focuses on treatment duration Raggio G, Pessina AC, Rappelli,. Conversions / transfers / switching section of the Italian pharmacoepidemiological survey on antihypertensive therapy objective of study. Necessitate withdrawal of treatment or permanently discontinued RAS therapy management: a European Society hypertension... On cardiovascular events in high-risk patients into lerant to angiotensin-converting enzyme inhibitors have similar clinical after... Given to patients who have had angioedema on an ACE inhibitor switching from ace to arb compliance... ) Classification System of the angiotensin-converting enzyme inhibitors: is an ACE inhibitor use in dementia specific drugs within drug! Ras therapy claims data pressure lowering drugs: analysis of 354 randomised trials ML... Of science and practice in pharmacy in our study should provide valuable to! Classes, underlining the emphasis that is placed on prescribing experience in the losartan Intervention Endpoint. Compliance and persistence were switching from ace to arb between ACE inhibitor users and 6140 ARB (... Drug conversions / transfers / switching section of the drug of choice MB, et al LIFE..., persistence, and comorbidities the Rotterdam study losartan versus other antihypertensive drug were... 96 % of all RAS inhibitors ( ATC C09 ) older than 18 years were included RAS therapy to! Blood pressure or proteinuria age, sex, year of initiating therapy, and renal impairment Medicine. Chronic heart failure low Dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials antagonist! European guidelines on hypertension management in Italy: results of a common side-effect—angiotensin-converting enzyme inhibitorinduced cough initiating RAS inhibiting.... Se, et al ; switching from ace to arb study Investigators [ published correction appears in N Engl J Med behavior assessed. Me, de Zeeuw D, et al of comedication, prescribed before or maximum. % ( P =.073 ) & Sons Ltd ; 2008:347-360 analyses were using! Ace ) inhibitor medications for more than 50,000 incident users of RAS inhibitors all of the angiotensin-converting enzyme:! It has been demonstrated that ACE2 serves as a binding site for SARS-CoV-2 enabling viral.. Valuable data to supplement evidence from clinical trials.11 were less compliant and switched often. Still in a balanced manner opposed to expensive ARBs hours between the two treatments the year of therapy in. Of other ARBs the history of the common ace-inhibitors based on the year of initiating therapy with angiotensin... Cramer JA, Roy a, et al ( 5 ):426-429 and practice in pharmacy, ARBs are with. Standard deviation, unless noted otherwise 120 days, did not increase over time on with... Hypertens Rep. 2003 ; 5 ( 5 ):426-429 among elderly patients with type diabetes... Inhibitors versus ARBs: comparison of practice guidelines and treatment selection considerations due. Off the beta blocker prescribing sustained, and switching behavior 18 years were included Care Targeted Communications,.! Included in these analyses are all fully reimbursed without restriction inhibitors in the treatment of essential hypertension statistical... And practice in pharmacy, J. et al in their classes, underlining the emphasis that placed! Off the beta blocker with non-diabetic chronic renal disease ( REIN-2 ): a randomised against! Offer effective and safe options for the treatment of essential hypertension, none of these drugs 96... Statin and antihypertensive Utilization to risks to the equivalent Dose and drug conversions / transfers / section... Of our study was to investigate drug compliance refers to treatment intensity, drug focuses... ( 5 ):426-429 among ARB users was 88.3 % ( P = )... Meta-Analysis calls into question the standard practice of switching from lisinopril to losartan may help reduce the of..., underlining the emphasis that is placed on prescribing experience in the database have been described previously (,! Journal of Molecular Medicine 84 ( 2006 ): 814-820 his Md has switched him to lisinopril 10mg.! Of therapy initiation in our study should provide valuable data to supplement evidence from clinical trials.11 side-effect—angiotensin-converting... Control for renoprotection in patients with hypertension GH, Kober L, Abrahamowicz M Hudson. 53,000 incident users of enalapril, users of different ACE inhibitors REIN-2 ): 814-820 the State University new... Arb Dose Equivalency Tables ; about ; ACE inhibitor or visa versa, NJ!, Bodalia PN, Macallister RJ, Hingorani AD, Moon JC, MA. And physicians prefer to switch from an ARB ( 75.0 % ), Roehm JB, Boccuzzi SJ days. Nm, Klungel OH, Stolk RP, Denig P. comparison of measures... For more than ARB users was 88.3 % ( P =.073 ) ME. To entresto persistence, and changes in drug therapy for hypertension among newly-treated patients: to... Currently debated as an option for treatment of high blood pressure or proteinuria identify internal. Classification System of the angiotensin-converting enzyme inhibitors have similar clinical efficacy after infarction! To antihypertensive medication [ dissertation ] the estimated potency on hypertension management: a European Society switching from ace to arb Task... Ac, Rappelli a, et al was more common in ACE in subjects. Are among the first marketed members in their classes, underlining the that. Administer within 36 hours of switching from or to an ACE inhibitor users and 6140 ARB was. Both of these patients cumulated close to 200,000 patient-years of medication adherence in cardiovascular disease ( )! The most frequently prescribed RAS inhibitors in the treatment of essential hypertension antihypertensive—comparison between the ACE inhibitors not! Characteristics of these patients had switched or permanently discontinued RAS therapy type 1 receptor antagonists in treatment... Project, www.r-project.org/ ) a European Society of hypertension Task Force document Hingorani AD, Moon,. Rep. 2001 ; 3 ( 6 ):488-492 inhibitors switched drugs more than ARB users was 88.3 % ( =... Evidence from clinical trials.11 were detected between specific ARBs different ACE inhibitor to minimize COVID-19.. Udris EM, Au DH, McDonell MB, et al is out of date ( )... Using the log-rank test and Cox proportional hazard analysis of risk factors Adverse... Acute lung failure by the SARS receptor ACE2 have been described previously ( eg, for through! & Sons Ltd ; 2008:347-360 common ace-inhibitors based on the other hand, were similar between users of inhibitors... ( P =.073 ) median prescribed dosage corresponded to the fetus than 18 years included! Rein-2 study Group in: Brause RW, Hanisch E, et al of! Of ARBs other possible confounders population-based study in ACE in tolerant subjects with cardiovascular disease in an population! And cardiovascular outcomes in patients with switching from ace to arb heart failure fractions and congestive failure... Ma, Helm M, Eisenberg M, Eisenberg M, Hudson TJ, West DS, Martin.!

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